The immunopathogenesis of a number of immune-mediated diseases and/or diseases characterized by abnormalities of immune function was investigated. Major histo-compatability complex (MHC) class II antigen expression by thyroid follicular cells was studied which demonstrated that these cells can function as antigen-presenting cells (APC) in Graves' disease (GD) and Hashimoto's thyroiditis (HT). These APC present surface autoantigens such as thyroglobulin (Tg) and microsomes (M) to T cells by virtue of their class II antigen expression. We demonstrated that recombinant Gamma-interferon (IFN) but not Alpha-IFN or interleukin-2 (IL-2) induced 80-100% thyroid follicular cells to express HLA-DR and about 50% to express HLA-DQ, strongly suggesting that IFN released during a viral infection or an ongoing immune response may contribute to the development of autoimmune thyroid disease in susceptible individuals. Using cell cloning technology, we demonstrated that the thyroid is infiltrated with autoreactive T cells in GD and HT and that these T cells can be expanded in vitro by IL-2. The proliferation of these clones in response to MHC Class II antigen-positive thyroid cells provides compelling evidence that these latter cells initiate or perpetuate the autoimmune process. Phagocytosis-inducing factor derived from patients with erythrophagocytosis and angiocentric lymphoproliferative disease as well as normals was biochemically characterized and its precise cell of origin was delineated. The natural killer cell defect in the Chediak-Higashi syndrome was corrected in vitro by IL-2. This has important potential therapeutic implications in this disease which is characterized by the development of lymphomas. We further characterized the components of the human eosinophil which play major roles in the pathogenesis of the idiopathic hypereosinophilic syndrome. We are continuing studies on the natural history, immunopathogenesis, and therapy of idiopathic dilated cardiomyopathy.